Rabies is an acute progressive encephalitis caused by infection with an RNA virus of the family Rhabdoviridae (genus lyssavirus). While human rabies fatalities are rare in developed nations (there are usually fewer than 5 deaths in the United States each year), significant numbers of deaths are reported in, for example, India, where 50,000 die of the disease and more than 500,000 are treated. Even in the United States, 15,000 to 40,000 people receive anti-rabies treatment each year. Typically, dogs are the major reservoirs of the disease but other mammals such as raccoon, skunk, bat, and fox are frequent reservoirs. Transmission of the virus from an animal reservoir to human usually occurs by a bite or scratch that penetrates the skin. Since rabies in humans is almost always fatal, even a suspected infection must be treated with an aggressive post-exposure treatment regimen.
The post-exposure treatment of rabies in humans consists of proper wound care, local administration of anti-rabies serum immunoglobulin infiltrated into and around the wound, and administration of multiple doses of rabies vaccine usually over several days and weeks (for a review of prophylaxis against rabies, see, e.g., Rupprecht and Gibbons et al., N Engl J Med 351:25 (2004)). Proper wound care can lessen the amount of virus that survives to enter the patient. Infiltration of the area with anti-rabies serum immunoglobulin can bind to the rabies virus and help clear it thereby lessening the viral load (by passive immunization). Administration of multiple does of rabies vaccine (active immunization), usually in the form of a first dose followed by subsequent booster doses, allow for the patient to produce a vigorous active immunity, including humoral and cellular responses. Current sources of anti-rabies serum immunoglobulin are obtained from the blood of vaccinated human donors. Other sources of anti-rabies serum immunoglobulin, for example, equine or murine, are considered unacceptable. Current sources of rabies vaccines are produced in cell lines and chemically inactivated and lyophilized. While these agents, when administered in time, are highly effective, certain obstacles remain.
For example, there are few manufacturers of these anti-rabies agents and they remain relatively expensive, especially in the developing world where they are most needed. In addition, human anti-rabies serum immunoglobulin, because it is harvested from the serum of human donors, must be highly purified to prevent the transmission of any adventitious agents. Moreover, the anti-rabies vaccine requires labor intensive cell culture and extensive inactivation and purification steps. Accordingly, improved immunotherapies for treating and preventing rabies infection are needed.